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Safety and Immunogenicity of 3 Lots of Cell-derived Subunit Influenza Vaccine as Compared to 1 Lot to Egg-derived Subunit Influenza Vaccine in Healthy Adults (>=18 to <=60)

Primary Purpose

Influenza

Status
Completed
Phase
Phase 3
Locations
Lithuania
Study Type
Interventional
Intervention
Cell-Derived Trivalent Subunit Influenza Vaccine Lot 1 (cTIV)
Cell-Derived Trivalent Subunit Influenza Vaccine Lot 2 (cTIV)
Cell-Derived Trivalent Subunit Influenza Vaccine Lot 3 (cTIV)
Egg-Derived Trivalent Subunit Influenza Vaccine (TIV)
Sponsored by
Novartis Vaccines
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Influenza focused on measuring Influenza, Flu, Cell-Derived, Egg-Derived, Healthy Adults, Safety, Immunogenicity, Vaccination

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: 18 to <61 years of age mentally competent to understand the nature, the scope and the consequences of the study able and willing to give written informed consent prior to study entry in good health as determined by: medical history, physical examination, clinical judgment of the Investigator. Exclusion Criteria: unwilling or unable to give written informed consent to participate in the study participation in another clinical trial of an investigational agent within 90 days prior to Visit 1 and throughout the entire study currently experiencing an acute infectious disease any serious disease, such as, for example: cancer, autoimmune disease (including rheumatoid arthritis), advanced arteriosclerotic disease or complicated diabetes mellitus, chronic obstructive pulmonary disease (COPD) requiring oxygen therapy, acute or progressive hepatic disease, acute or progressive renal disease, congestive heart failure surgery planned during the study period bleeding diathesis history of hypersensitivity to any component of the study medication or chemically related substances history of any anaphylaxis, serious vaccine reactions, or allergy to any of the vaccine component known or suspected impairment/alteration of immune function, for example resulting from: receipt of immunosuppressive therapy (any corticosteroid therapy or cancer chemotherapy), receipt of immunostimulants, receipt of parenteral immunoglobulin preparation, blood products, and/or plasma derivates within 3 months prior to Visit 1 or planned during the full length of the study, high risk for developing an immunocompromising disease history of drug or alcohol abuse laboratory-confirmed influenza disease within 6 months prior to Visit 1 receipt of influenza vaccine within 6 months prior to Visit 1 receipt of another vaccine within 60 days prior to Visit 1, or planned vaccination within 3 weeks following study vaccination any acute respiratory disease or infections requiring systemic antibiotic or antiviral therapy (chronic antibiotic therapy for urinary tract prophylaxis is acceptable) or experienced fever (i.e., axillary temperature ≥ 38 degree C) within 5 days prior to Visit 1 if female, pregnant or breastfeeding if female, refusal to use a reliable contraceptive method during the three weeks following vaccination planned relocation abroad during the study period any condition that, in the opinion of the Investigator, might interfere with the evaluation of the study objectives.

Sites / Locations

  • 2nd Department of Internal Diseases, Panevezys Hospital,
  • Dept. Infectious Diseases and Microbiology of Vilnius University

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Active Comparator

Arm Label

cTIV_lot 1

cTIV_lot 2

cTIV_lot 3

TIV group

Arm Description

Outcomes

Primary Outcome Measures

Geometric Mean Titers After One Dose of Cell Culture-derived or the Egg-derived Influenza Vaccine in Adult Subjects
The haemagglutinin Inhibition (HI) antibody titer response following one dose of cTIV for each of the three lots separately and one dose of cTIV (combined) compared to TIV is reported as Geometric mean titers (GMTs). The HI GMTs were evaluated using egg-derived antigen assay.
Geometric Mean Ratios After One Dose of Cell Culture-derived or the Egg-derived Influenza Vaccine in Adult Subjects
Immunogenicity was assessed in terms of Geometric Mean Ratio (GMR) following one dose of cTIV for each of the three vaccine lots separately and for one dose of cTIV (combined) compared to TIV, according to the CHMP criterion. The European licensure (CHMP) criterion is met if the mean geometric increase (GMR, day 22/day 1) in HI antibody titer is >2.5.
Percentage of Subjects With HI Titers ≥40
Immunogenicity was assessed in terms of percentage of adult subjects achieving HI titers ≥40, after one dose of cTIV for each of the three vaccine lots separately and for one dose of cTIV (combined) compared to TIV, according to the CHMP criterion. European Licensure (CHMP) criterion is met if the percentage of subjects achieving HI titers ≥40 is >70%.
Percentage of Subjects With Seroconversion or Significant Increase in HI Antibody Titers After One Dose of Either Cell-derived or Egg-derived Subunit Trivalent Influenza Vaccine
Immunogenicity was assessed in terms of percentage of adult subjects showing seroconversion or significant increase in HI antibody titers after one dose of cTIV for each of the three vaccine lots separately and one dose of cTIV (combined) compared to TIV, according to the CHMP criterion. European Licensure (CHMP) criterion is met if the percentage of subjects achieving seroconversion or significant increase is >40%. As per European Licensure (CHMP) criterion seroconversion is defined as percentage of subjects with a prevaccination HI titer <10 to a postvaccination titer ≥40; whereas, significant increase is defined as HI titer ≥10 prevaccination and ≥4-fold Hi titer increase post-vaccination.

Secondary Outcome Measures

Number of Subjects Reporting Solicited Adverse Events After One Dose of Cell Culture-derived or the Egg-derived Influenza Vaccine.
To assess the safety and tolerability in terms of number of subjects reporting solicited adverse events following one injection of one dose of cTIV for each of the three vaccine lots separately and for one dose of cTIV (combined) compared to TIV.
Safety Data of Subjects Upto Six Months After One Dose of Cell Culture Derived or Egg-derived Influenza Vaccine
Additional safety data from day 1 through day 181 after one dose of cTIV (combined) or TIV in terms of serious adverse events (SAEs), adverse events (AEs) necessitating a physician's visit and/or resulting in premature subject's withdrawal from study is reported.

Full Information

First Posted
April 3, 2006
Last Updated
August 2, 2019
Sponsor
Novartis Vaccines
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1. Study Identification

Unique Protocol Identification Number
NCT00310804
Brief Title
Safety and Immunogenicity of 3 Lots of Cell-derived Subunit Influenza Vaccine as Compared to 1 Lot to Egg-derived Subunit Influenza Vaccine in Healthy Adults (>=18 to <=60)
Official Title
A Phase III, Randomized, Controlled, Observer-Blind, Multi-Center Study to Evaluate Safety, Tolerability and Immunogenicity of a Single Intramuscular Dose of Three Lots of a Trivalent Subunit Influenza Vaccine Produced in Mammalian Cell Culture Or of a Trivalent Subunit Influenza Vaccine Produced in Embryonated Hen Eggs, in Healthy Adult Subjects Aged >=18 to <=60
Study Type
Interventional

2. Study Status

Record Verification Date
August 2019
Overall Recruitment Status
Completed
Study Start Date
September 2005 (undefined)
Primary Completion Date
October 2005 (Actual)
Study Completion Date
April 2006 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Vaccines

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The present study aims to evaluate safety, tolerability and immunogenicity of three lots of Chiron's cell-derived subunit influenza vaccine in healthy adult subjects as compared to a conventional egg-derived control vaccine licensed in Europe.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Influenza
Keywords
Influenza, Flu, Cell-Derived, Egg-Derived, Healthy Adults, Safety, Immunogenicity, Vaccination

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
1200 (Actual)

8. Arms, Groups, and Interventions

Arm Title
cTIV_lot 1
Arm Type
Experimental
Arm Title
cTIV_lot 2
Arm Type
Experimental
Arm Title
cTIV_lot 3
Arm Type
Experimental
Arm Title
TIV group
Arm Type
Active Comparator
Intervention Type
Biological
Intervention Name(s)
Cell-Derived Trivalent Subunit Influenza Vaccine Lot 1 (cTIV)
Intervention Description
One single 0.5ml intramuscular injection of Cell Derived Trivalent Subunit Influenza Vaccine (cTIV) from Lot 1
Intervention Type
Biological
Intervention Name(s)
Cell-Derived Trivalent Subunit Influenza Vaccine Lot 2 (cTIV)
Intervention Description
One single 0.5ml intramuscular injection of Cell Derived Trivalent Subunit Influenza Vaccine (cTIV) from Lot 2
Intervention Type
Biological
Intervention Name(s)
Cell-Derived Trivalent Subunit Influenza Vaccine Lot 3 (cTIV)
Intervention Description
One single 0.5ml intramuscular injection of Cell Derived Trivalent Subunit Influenza Vaccine (cTIV) from Lot 3
Intervention Type
Biological
Intervention Name(s)
Egg-Derived Trivalent Subunit Influenza Vaccine (TIV)
Intervention Description
One single 0.5ml intramuscular injection of Egg Derived Trivalent Subunit Influenza Vaccine (TIV).
Primary Outcome Measure Information:
Title
Geometric Mean Titers After One Dose of Cell Culture-derived or the Egg-derived Influenza Vaccine in Adult Subjects
Description
The haemagglutinin Inhibition (HI) antibody titer response following one dose of cTIV for each of the three lots separately and one dose of cTIV (combined) compared to TIV is reported as Geometric mean titers (GMTs). The HI GMTs were evaluated using egg-derived antigen assay.
Time Frame
Day 22 postvaccination
Title
Geometric Mean Ratios After One Dose of Cell Culture-derived or the Egg-derived Influenza Vaccine in Adult Subjects
Description
Immunogenicity was assessed in terms of Geometric Mean Ratio (GMR) following one dose of cTIV for each of the three vaccine lots separately and for one dose of cTIV (combined) compared to TIV, according to the CHMP criterion. The European licensure (CHMP) criterion is met if the mean geometric increase (GMR, day 22/day 1) in HI antibody titer is >2.5.
Time Frame
Day 22 postvaccination
Title
Percentage of Subjects With HI Titers ≥40
Description
Immunogenicity was assessed in terms of percentage of adult subjects achieving HI titers ≥40, after one dose of cTIV for each of the three vaccine lots separately and for one dose of cTIV (combined) compared to TIV, according to the CHMP criterion. European Licensure (CHMP) criterion is met if the percentage of subjects achieving HI titers ≥40 is >70%.
Time Frame
Day 22 postvaccination
Title
Percentage of Subjects With Seroconversion or Significant Increase in HI Antibody Titers After One Dose of Either Cell-derived or Egg-derived Subunit Trivalent Influenza Vaccine
Description
Immunogenicity was assessed in terms of percentage of adult subjects showing seroconversion or significant increase in HI antibody titers after one dose of cTIV for each of the three vaccine lots separately and one dose of cTIV (combined) compared to TIV, according to the CHMP criterion. European Licensure (CHMP) criterion is met if the percentage of subjects achieving seroconversion or significant increase is >40%. As per European Licensure (CHMP) criterion seroconversion is defined as percentage of subjects with a prevaccination HI titer <10 to a postvaccination titer ≥40; whereas, significant increase is defined as HI titer ≥10 prevaccination and ≥4-fold Hi titer increase post-vaccination.
Time Frame
Day 22 postvaccination
Secondary Outcome Measure Information:
Title
Number of Subjects Reporting Solicited Adverse Events After One Dose of Cell Culture-derived or the Egg-derived Influenza Vaccine.
Description
To assess the safety and tolerability in terms of number of subjects reporting solicited adverse events following one injection of one dose of cTIV for each of the three vaccine lots separately and for one dose of cTIV (combined) compared to TIV.
Time Frame
Day 1 to Day 7 postvaccination
Title
Safety Data of Subjects Upto Six Months After One Dose of Cell Culture Derived or Egg-derived Influenza Vaccine
Description
Additional safety data from day 1 through day 181 after one dose of cTIV (combined) or TIV in terms of serious adverse events (SAEs), adverse events (AEs) necessitating a physician's visit and/or resulting in premature subject's withdrawal from study is reported.
Time Frame
Day 1 - Day 181 postvaccination

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 18 to <61 years of age mentally competent to understand the nature, the scope and the consequences of the study able and willing to give written informed consent prior to study entry in good health as determined by: medical history, physical examination, clinical judgment of the Investigator. Exclusion Criteria: unwilling or unable to give written informed consent to participate in the study participation in another clinical trial of an investigational agent within 90 days prior to Visit 1 and throughout the entire study currently experiencing an acute infectious disease any serious disease, such as, for example: cancer, autoimmune disease (including rheumatoid arthritis), advanced arteriosclerotic disease or complicated diabetes mellitus, chronic obstructive pulmonary disease (COPD) requiring oxygen therapy, acute or progressive hepatic disease, acute or progressive renal disease, congestive heart failure surgery planned during the study period bleeding diathesis history of hypersensitivity to any component of the study medication or chemically related substances history of any anaphylaxis, serious vaccine reactions, or allergy to any of the vaccine component known or suspected impairment/alteration of immune function, for example resulting from: receipt of immunosuppressive therapy (any corticosteroid therapy or cancer chemotherapy), receipt of immunostimulants, receipt of parenteral immunoglobulin preparation, blood products, and/or plasma derivates within 3 months prior to Visit 1 or planned during the full length of the study, high risk for developing an immunocompromising disease history of drug or alcohol abuse laboratory-confirmed influenza disease within 6 months prior to Visit 1 receipt of influenza vaccine within 6 months prior to Visit 1 receipt of another vaccine within 60 days prior to Visit 1, or planned vaccination within 3 weeks following study vaccination any acute respiratory disease or infections requiring systemic antibiotic or antiviral therapy (chronic antibiotic therapy for urinary tract prophylaxis is acceptable) or experienced fever (i.e., axillary temperature ≥ 38 degree C) within 5 days prior to Visit 1 if female, pregnant or breastfeeding if female, refusal to use a reliable contraceptive method during the three weeks following vaccination planned relocation abroad during the study period any condition that, in the opinion of the Investigator, might interfere with the evaluation of the study objectives.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Vaccines
Organizational Affiliation
Novartis Vaccines & Diagnostics
Official's Role
Study Chair
Facility Information:
Facility Name
2nd Department of Internal Diseases, Panevezys Hospital,
City
Panevezys
Country
Lithuania
Facility Name
Dept. Infectious Diseases and Microbiology of Vilnius University
City
Vilnius
Country
Lithuania

12. IPD Sharing Statement

Citations:
PubMed Identifier
19666152
Citation
Ambrozaitis A, Groth N, Bugarini R, Sparacio V, Podda A, Lattanzi M. A novel mammalian cell-culture technique for consistent production of a well-tolerated and immunogenic trivalent subunit influenza vaccine. Vaccine. 2009 Oct 9;27(43):6022-9. doi: 10.1016/j.vaccine.2009.07.083. Epub 2009 Aug 8.
Results Reference
result

Learn more about this trial

Safety and Immunogenicity of 3 Lots of Cell-derived Subunit Influenza Vaccine as Compared to 1 Lot to Egg-derived Subunit Influenza Vaccine in Healthy Adults (>=18 to <=60)

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